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GSE38264
Mus musculus, Homo sapiens
51 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Bladder cancer (BC) is a highly prevalent human disease in which Rb pathway inactivation and epigenetic alterations are common events. However, the connection between these two processes is still poorly understood. Here we show that the in vivo inactivation of all Rb family genes in the mouse urothelium is sufficient to initiate BC development. The characterization of the mouse tumors revealed multiple molecular features of human BC, including the activation of E2F transcription factor and subsequent Ezh2 expression, and the activation of several signaling pathways previously identified as highly relevant in urothelial tumors. Whole transcriptional characterizations of the mouse bladder tumors revealed a significant overlap with human BC samples, and a predominant role for Ezh2 in the downregulation of gene expression programs. Importantly, we determined that in human superficial BC patients, the increased tumor recurrence and progression in these recurrences is associated with increased E2F and Ezh2 expression and Ezh2-mediated gene expression repression. Collectively, our studies provide a genetically defined model for human high-grade superficial BC and demonstrate the existence of an Rb-E2F-Ezh2 axis in bladder whose disruption can promote tumor development.
Publication Title
In vivo disruption of an Rb-E2F-Ezh2 signaling loop causes bladder cancer.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Genome-wide alternative splice analysis of RNA from lupus and its severe form lupus nephritis
Publication Title
Genome-wide peripheral blood transcriptome analysis of Arab female lupus and lupus nephritis.
Sample Metadata Fields
Sex, Specimen part, Disease stage
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Enzalutamide (formerly MDV3100 and available commercially as Xtandi), a novel androgen receptor (AR) signaling inhibitor, blocks the growth of castration-resistant prostate cancer (CRPC) in cellular model systems and was shown in a clinical study to increase survival in patients with metastatic CRPC. Enzalutamide inhibits multiple steps of AR signaling: (1) binding of androgens to AR, (2) AR nuclear translocation, and (3) association of AR with DNA.
Publication Title
Enzalutamide, an androgen receptor signaling inhibitor, induces tumor regression in a mouse model of castration-resistant prostate cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Xenopus laevis
- 9 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
ADAMs are transmembrane metalloproteases that control cell behavior by cleaving both cell adhesion and signaling molecules. The cytoplasmic domain of ADAMs can regulate the proteolytic activity by controlling the subcellular localization and/or the activation of the protease domain. Here we show that the cytoplasmic domain of ADAM13 is cleaved and translocates into the nucleus. Preventing this translocation renders the protein incapable of promoting cranial neural crest (CNC) cell migration in vivo, without affecting its proteolytic activity. In addition, the cytoplasmic domain of ADAM13 regulates the expression of multiple genes in the CNC. This study shows that the cytoplasmic domain of ADAM metalloproteases can perform essential functions in the nucleus of cells and may contribute substantially to the overall function of the protein.
Publication Title
Translocation of the cytoplasmic domain of ADAM13 to the nucleus is essential for Calpain8-a expression and cranial neural crest cell migration.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We aim to identify genes differentially expressed between mouse WT and COUP-TFI_Nex-Cre mutant cortices.
Publication Title
Postmitotic control of sensory area specification during neocortical development.
Sample Metadata Fields
Specimen part
View Samples- Citrus sinensis
- 6 Downloadable Samples
- Affymetrix Citrus Genome Array (citrus)
Description
The goal of the microarray experiment was to identify genes that were differentially expressed in NAD-treated and water-treated sweet orange leaf tissues. Results indicated that, compared with the water treatment, the NAD tretament triggered profound transcriptome changes in the citrus leaves, with about 1,200 genes being up-regulated or down-regulated by twofold or more.
Publication Title
Exogenous Nicotinamide Adenine Dinucleotide Induces Resistance to Citrus Canker in Citrus.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cellular identity is determined by its gene expression programs. The ability of the cell to change its identity and produce cell types outside its lineage is achieved by the activity of transcription controllers capable of reprogramming differentiation gene networks. The synovial sarcoma associated protein, SYT-SSX2, reprograms myogenic progenitors and human bone marrow-derived mesenchymal stem cells (BMMSCs) by dictating their commitment to a pro-neural lineage. It fulfills this function by directly targeting an extensive array of neural-specific genes as well as genes of developmental pathway mediators. Concomitantly, the ability of both myoblasts and BMMSCs to differentiate into their normal myogenic and adipogenic lineages was compromised. Synovial sarcoma is believed to arise in mesenchymal stem cells where formation of the t(X;18) translocation product, SYT-SSX, constitutes the primary event in the cancer. SYT-SSX is therefore believed to initiate tumorigenesis in its target stem cell. The data presented here allow a glimpse at the initial events that likely occur when SYT-SSX2 is first expressed and its dominant function in subverting the nuclear program of the stem cell, leading to its aberrant differentiation, as a first step toward transformation. In addition, we identified the fibroblast growth factor receptor gene, Fgfr2, as one occupied and upregulated by SYT-SSX2. Knockdown of FGFR2 in both BMMSCs and synovial sarcoma cells abrogated their growth and attenuated their neural phenotype. These results support the notion that the SYT-SSX2 nuclear function and differentiation effects are conserved throughout sarcoma development and are required for its maintenance beyond the initial phase. They also provide the stem cell regulator, FGFR2 as a promising candidate target for future synovial sarcoma therapy.
Publication Title
Reprogramming of mesenchymal stem cells by the synovial sarcoma-associated oncogene SYT-SSX2.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Synovial sarcoma is a rare malignancy characterized by the presence of a specific chromosomal translocation t(X;18) that results in the formation of a fusion protein SYT-SSX. Because it is believed that synovial sarcoma arises from mesenchymal stem or progenitor cells, we wanted to determine the changes in gene expression caused by SYT-SSX2 in untransformed mesenchymal progenitor cells - murine C2C12 myoblasts in this experiment.
Publication Title
Reprogramming of mesenchymal stem cells by the synovial sarcoma-associated oncogene SYT-SSX2.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Chronic myeloid leukemia is a disease originated at the level of hematopoietic stem cell, characterized by the abnormal overproduction and accumulation, both in blood and bone marrow, of myeloid cells. Treatment options include tyrosine kinase inhibitors that inhibit BCR-ABL activity, however some patients develop resistance to these drugs and has been asociated to the stem cells
Publication Title
Global gene expression profiles of hematopoietic stem and progenitor cells from patients with chronic myeloid leukemia: the effect of in vitro culture with or without imatinib.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina Genome Analyzer II
Description
During normal or pathological epithelial-to-mesenchymal transition, epithelium-specific gene expression is shut down, with the DNA-binding factor ZEB1 acting as a master suppressor of epithelial identity. Here, we show that ZEB1 occupies primate-specific tandem repeats (TRs) harboring dozens of copies of its DNA-binding motif and located within genomic loci relevant for epithelial identity. Deletion of one such repeat in a quasi-mesenchymal human cancer cell line induced the reacquisition of epithelial features and phenocopied the effects of ZEB1 gene deletion. Since ZEB1 binds clustered motifs in a non-cooperative manner, changes in its nuclear concentration enable graded adjustments of TR occupancy, thus fine-tuning repression level. In addition, high motif density in TRs allows ZEB1 binding (and shutdown of epithelial programs) despite differences in chromatin organization and accessibility among epithelial cell types. Overall design: Total RNA from human pancreatic ductal adenocarcinoma cell lines was processed for multiparallel sequencing. Experiments were carried out in genome edited clonal MiaPaCa2 cells (3 ZEB1-deleted CRISPR-Cas9 clones and 3 wt clones).
Publication Title
Co-optation of Tandem DNA Repeats for the Maintenance of Mesenchymal Identity.
Sample Metadata Fields
Cell line, Subject
View Samples